Increasing adipose cell size in the aging rat model of obesity is accompanied by both a decreasing ability of insulin to stimulate glucose transport activity and a decreasing capacity of the cell to metabolize glucose. The mechanism of the former alteration has been examined by measuring the number of functional glucose transport systems with an equilibrium 3H-cytochalasin B binding assay in purified plasma membrane prepared from isolated adipose cells of widely varying size which have been incubated in vitro in the absence or presence of insulin. While the number of functional glucose transport systems/mg plasma membrane protein in the basal state remains constant, the number of insulin-stimulatable systems decreased with increasing cell size in proportion to insulin's decreasing ability to stimulate transport activity in the intact cell. The mechanism of the latter alteration has been examined by estimating the activities of the specific pathways for glucose carbon metabolism in intact adipose cells of widely varying size through the use of increasing concentrations of differentially radiolabeled glucose in the presence of increasing insulin concentrations. Increasing cell size is accompanied by markedly decreasing de novo fatty acid synthesis and hexose monophosphate shunt activity and increasing endogenous fatty acid reesterification.